The effects of nitrous oxide, enflurane, and isoflurane on cortical somatosensory evoked potentials (SEPs) were studied in 29 patients undergoing intracranial or spinal operations. Anesthesia was induced with fentanyl (25 μg/kg, iv) plus thiopental (0.5–1.0 mg/kg, iv). In one group of patients (n = 12), nitrous oxide (50%) was compared with enflurane (0.25–1.0%), and in another group (n = 12) nitrous oxide (50%) was compared with enflurane (0.25–1.0%). In all third group of patients (n = 5) with preexisting neurologic deficits, nitrous oxide (50%) was compared with enflurane (0.25–1.0%). In all three groups, one gas was administered for 30 min, and then the alternate gas was administered for 30 min; then the cycle was repeated for a total of two administrations of each of the two anesthetics. SEPs were determined before and after induction of anesthesia and at the end of each 30-min study period. The latencies and amplitudes of the early cortical components of the upper- and lower-extremity SEP were examined. Induction of anesthesia resulted in increases of latency in both upper- and lower-extremity SEPs-without any alteration of amplitude. Nitrous oxide, enflurane, and isoflurane each decreased the amplitude of the upper-extremity SEPs compared with the postinduction value. The amplitude of the upper-extremity SEPs was less during nitrous oxide than with either enflurane or isoflurane. Nitrous oxide decreased the amplitude of lower-extremity SEPs below postinduction value, while enflurane and isoflurane had no effect. Isoflurane and enflurane increased the latency of both upper- and lower-extremity SEPs slightly, while nitrous oxide had no effect. In patients with preexisting neurologic deficits, nitrous oxide decreased amplitude more than enflurane. The authors conclude that during fentanyl-based anesthesia either enflurane or isoflurane (0.25–1.0%) results in less alteration of cortical SEPs than does nitrous oxide (50%), and these concentrations of enflurane or isoflurane are compatible with the generation of waves that are adequate for evaluation.